2. Academic Validation
  3. Discovery of a nanomolar inhibitor of the human murine double minute 2 (MDM2)-p53 interaction through an integrated, virtual database screening strategy

Discovery of a nanomolar inhibitor of the human murine double minute 2 (MDM2)-p53 interaction through an integrated, virtual database screening strategy

  • J Med Chem. 2006 Jun 29;49(13):3759-62. doi: 10.1021/jm060023+.
Yipin Lu 1,  Zaneta Nikolovska-Coleska,  Xueliang Fang,  Wei Gao,  Sanjeev Shangary,  Su Qiu,  Dongguang Qin,  Shaomeng Wang
Affiliations

Affiliation

  • 1 Comprehensive Cancer Center and Department of Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109, USA.
PMID: 16789731 DOI: 10.1021/jm060023+
Abstract

An integrated, virtual database screening strategy has led to 7-[anilino(phenyl)methyl]-2-methyl-8-quinolinol (4, NSC 66811) as a novel inhibitor of the murine double minute 2 (MDM2)-p53 interaction. This quinolinol binds to MDM2 with a Ki of 120 nM and activates p53 in Cancer cells with a mechanism of action consistent with targeting the MDM2-p53 interaction. It mimics three p53 residues critical in the binding to MDM2 and represents a promising new class of non-peptide inhibitors of the MDM2-p53 interaction.

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